STANFORD, Calif. -- Severe stress can damage a child's brain, say researchers at the Stanford University School of Medicine and Lucile Packard Children's Hospital. The researchers found that children with post-traumatic stress disorder and high levels of the stress hormone cortisol were likely to experience a decrease in the size of the hippocampus - a brain structure important in memory processing and emotion.

Although similar effects have been seen in animal studies, this is the first time the findings have been replicated in children. The researchers focused on kids in extreme situations to better understand how stress affects brain development.

"We're not talking about the stress of doing your homework or fighting with your dad," said Packard Children's child psychiatrist Victor Carrion, MD. "We're talking about traumatic stress. These kids feel like they're stuck in the middle of a street with a truck barreling down at them."

Carrion, assistant professor of child and adolescent psychiatry at the medical school and director of Stanford's early life stress research program, and his collaborators speculate that cognitive deficits arising from stress hormones interfere with psychiatric therapy and prolong symptoms.

The children in the study were suffering from post-traumatic stress disorder, or PTSD, as a result of undergoing physical, emotional or sexual abuse, witnessing violence or experiencing lasting separation and loss. This type of developmental trauma often impairs the child's ability to reach social, emotional and academic milestones.

"We'd really like to understand why some children are more resilient than others, and what the long-term effects of extreme stress are," said Carrion, who is the first author of the research, to be published in the March issue of Pediatrics. "We know, for example, that these children are at higher risk of developing depression and/or anxiety as adults."

One theory posits that everyone carries an ongoing stress burden that accumulates throughout life. Once a certain threshold is reached, either through one or two very traumatic events or through chronic, high levels of stress, adults and children can begin to exhibit PTSD symptoms such as re-experience (including flashbacks, intrusive thoughts or nightmares), avoidance and emotional numbing, and physiological hyperarousal (such as an elevated resting heart rate). These behavioral symptoms make PTSD difficult to differentiate from other conditions such as attention deficit/hyperactivity disorder.

Children predisposed by genetics or environment to be more anxious than their peers are also more likely to develop PTSD in response to emotional trauma, perhaps because their responses to other life experiences simply left them closer to that threshold than less-anxious children.

The researchers studied 15 children from ages 7 to 13 suffering from PTSD. They measured the volume of the hippocampus at the beginning and end of the 12- to 18-month study period. After correcting for gender and for physiological maturity, they found that kids with more severe PTSD symptoms and higher bedtime cortisol levels (another marker of stress) at the start of the study were more likely to have reductions in their hippocampal volumes at the end of the study than their less-affected, but still traumatized peers.

It is significant that the change in the hippocampal volume corresponds to both PTSD symptom severity and increased cortisol levels. Cortisol belongs to a class of human hormones known as glucocorticoids that have been shown to kill hippocampal cells in animals. In a vicious cycle, a reduction in hippocampal size can make it more difficult for a child to process and deal with traumatic events, which in turn may raise both stress and cortisol levels that cause even more damage.

"Although everyday levels of stress are necessary to stimulate normal brain development, excess levels can be harmful," said Carrion, likening the biological effects of increasing amounts of stress to an inverted U. "One common treatment for PTSD is to help a sufferer develop a narrative of the traumatic experience. But if the stress of the event is affecting areas of the brain responsible for processing information and incorporating it into a story, that treatment may not be as effective."

Carrion and his colleagues are now using an imaging technique known as functional MRI to visualize whether and how the children's brains differ when performing emotional and cognitive tasks.

"What we have now is basically a snapshot," said Carrion. "We can't yet say much about function. But we know that PTSD is chronic and pervasive. Hopefully with further research we can develop more effective, targeted interventions to help these kids."

The study was funded by the National Institutes of Health, the National Alliance for Research on Schizophrenia and Depression, the American Foundation for Suicide Prevention and the Aloha Foundation.

Other co-authors include professor of psychiatry Allan Reiss, MD, and former postdoctoral scholar Carl Weems, PhD, who is now an associate professor of psychology at the University of New Orleans.

Stanford University Medical Center integrates research, medical education and patient care at its three institutions - Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital at Stanford. For more information, please visit the Web site of the medical center's Office of Communication & Public Affairs at http://mednews.stanford.edu.

Ranked as one of the best pediatric hospitals in the nation by U.S.News & World Report and Child magazine, Lucile Packard Children's Hospital at Stanford is a 264-bed hospital devoted to the care of children and expectant mothers. Providing pediatric and obstetric medical and surgical services and associated with the Stanford University School of Medicine, Packard Children's offers patients locally, regionally and nationally the full range of health care programs and services - from preventive and routine care to the diagnosis and treatment of serious illness and injury. For more information, visit http://www.lpch.org.

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